E10A for the Treatment of Squamous Cell Carcinoma of the Head and Neck

Head and Neck Neoplasms Clinical Trial

Official title:

A Randomized, Open-label, Multi-center Phase III Study Designed to Evaluate the Safety and Efficacy of E10A in Patients With Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck Region

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02630264
• Other study ID #: E10AIII
• Status: Recruiting
• Phase: Phase 3
• First received: December 26, 2013
• Last updated: December 10, 2015
• Start date: June 2013
• Est. completion date: December 2016

Study information

• Verified date: December 2015
• Source: Guangzhou Double Bioproducts Co., Ltd
• Contact: Huiqiang Huang, Ph.d
• Phone: (86)2087343350
• Email: huanghq[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. After transfection tumor cells. E10A expresses human endostatin, which inhibits vascular endothelial cell proliferation and tumor angiogenesis, and blocks tumor blood supply, thereby specifically inhibiting tumor growth and inducing apoposis of tumor cells. Both pre-clinical and animal models have demonstrated the anti-tumor activities of E10A. The safety and efficacy of E10A in treating head and neck cancer has also been demonstrated in Phase I and Phase II studies.

Description:

Phase II Clinical Study From March 2008 to December 2010 Safety and efficacy of intratumoral injections of E10A to cisplatin and paclitaxel was evaluated a multicenter, open-label, randomized clinical study in patients with advanced head and neck squamous cell carcinoma.

136 eligible patients were recruited and randomly assigned. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 21 for a maximum of six cycles or to receive chemotherapy only.

The primary end point was the objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion. The secondary end points were the objective disease control rate (DCR, or stable disease (SD) + PR + CR at the target tumor lesion), the overall RR, the overall DCR, OS, and progression-free survival (PFS).

The administration of E10A benefited some subgroups of patients. In the HNSCC patients, the objective RR was 36.5% (15/41) with E10A administration, exhibiting a trend of exceeding the rate of 20.0% (7/35) in the control group (P = 0.090; OR: 0.43), whereas the objective RR was 44.4% (12/27) versus 40.6% (13/32) in the NPC patients (P = 0.487; OR: 0.86). Patients who had previously received chemotherapy in the E10A group had a 44.8% (12/29) objective RR, whereas patients in the control group had only a 22.6% objective RR (7/31; P = 0.06, OR: 0.36). In contrast, patients without previous chemotherapy had a similar RR in both groups (34.3 versus 39.4%; P = 0.426, OR: 1.25).

The difference in the Kaplan-Meier estimates of PFS favored chemotherapy plus E10A, which resulted in a 3.43-month improvement. With a median follow-up of 10.47 months, the median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03 months (interquartile range: 3.27-13.73) in the E10A group. As The median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03months (interquartile range: 3.27-13.73) in the E10A group.

The OS of the E10A group was relatively prolonged in different subgroups compared with the controls (e.g., 13.37 months versus 9.67 months in the HNSCC patients, 13.03 months versus 10.50 months in those who had received prior treatment; Figure 1), but these results did not translate into significantly superior survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 540
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients older than 18 years with histologically or cytologically proven locoregionally advanced or metastatic HNSCC (excluding NPC) not suitable for operation or radiotherapy

2. A life expectancy?12 weeks.

3. Patients were required to have at least one measurable (by imaging or photograph complied RECIST) lesion with the largest diameter ?2 cm and suitable for the intratumoral injection of E10A,

4. Not received chemotherapy, radiotherapy, or biotherapy within 4 weeks.

5. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2.

6. Adequate bone marrow,renal, and liver functions.

Exclusion Criteria:

1. Known allergies to the study drug.

2. The presence of important blood vessels/nerves or ulceration in the target lesion not suitable for injection.

3. Tumor relapses within 6 months after paclitaxel chemotherapy.

4. Severe coagulation disorders or bleeding tendency.

5. Severe uncontrolled medical conditions.

6. Recent history of myocardial infarction acute infection, pregnancy or lactation, or symptomatic brain metastases

7. A history of corticosteroids or immunosuppressives use within four weeks of study entry

8. Received any chemotherapy or radiotherapy within four weeks of study entry

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Neoplasms

Intervention

Drug:
• Endostatins
Specification: 1mL/division, 1×1012 VP/1.0mL E10A preparation: Thaw frozen E10A stored at -20°C vials at room temperature until E10A is liquid. Swirl gently. Do NOT shake. Method of administration E10A was diluted with 0.9% sodium chloride to appropriate dose according to the longest diameter of the target lesion. After local anesthesia, we penetrated the syringe under normal skin subcutaneously 5 mm into the tumor or vertically into the lymph node under direct visualization and withdrew it to confirm the absence of blood. Applied local compression for 10 minutes and pasted a sterile sticker on the injection site to avoid bleeding.
• Paclitaxel injection
Specification: 30mg/5mL, Usage: 160mg/m2 on day 3, according to instruction.
• Cisplatin injection
Specification: 20mg Usage: Cisplatin 25mg/ m2 on day 3, 4, and 5,according to instruction.

Locations

Country	Name	City	State
China	Guangzhou DB	Gaungzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Double Bioproducts Co., Ltd

Country where clinical trial is conducted

China, 

References & Publications (2)

Lin X, Huang H, Li S, Li H, Li Y, Cao Y, Zhang D, Xia Y, Guo Y, Huang W, Jiang W. A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors. Cancer Biol Ther. 2007 May;6(5):648-53. Epub 2007 Feb 13. — View Citation

Ye W, Liu R, Pan C, Jiang W, Zhang L, Guan Z, Wu J, Ying X, Li L, Li S, Tan W, Zeng M, Kang T, Liu Q, Thomas GR, Huang M, Deng W, Huang W. Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression	Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time	Up to 24 weeks	No
Secondary	Change in Overall response rate (CR+PR)	the end of every 2 treatment cycles (each cycle is 21 days), and every 3 months during follow-up until disease progression. objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion.	Up to 24 weeks, from date of randomization until the date of first documented progression	No
Secondary	Chang in disease control rate (CR+PR+SD)	the end of every 2 treatment cycles(each cycle is 21 days), and every 3 months during follow-up until disease progression.The CR or PR patients were reconfirmed	Up to 24 weeks, From date of randomization until the date of first documented progression	No
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)	All adverse events were recorded regardless of their relevance to E10A	Up to 32 weeks, from date of randomization until the date of first documented progression or date	Yes
Secondary	Overall survival	from cycle 2 to cycle 4 and calculated the survival during follow-up	Up to 24 month, through study completion	Yes